News Archive - Progress Newsletter Fall, 1999 Online

Cancer Center Launches Major International Colon Cancer Study

Researchers at the University of Michigan Comprehensive
Cancer Center and the KHC National Center of Cancer Control
in Haifa, Israel have been awarded a $4.8 million grant to
study genetic aspects of colon cancer. The five-year study,
funded by the National Cancer Institute, will examine how
genetic susceptibility to cancer may be modified by diet,
medications and lifestyle.

The Molecular Epidemiology of Colorectal Cancer study will
identify and interview more than 2,000 individuals in Israel
who have colon cancer and compare them to a cancer-free group
of equal size. Investigators hope to learn why some people
who carry genes that increase their risk of colon cancer develop
tumors while others with the same gene do not.

"Colon cancer is a complex disease, and genetic susceptibility
is only part of the story," says Stephen Gruber, M.D., Ph.D.,
principal investigator of the study and director of the Cancer
Genetics Clinic. "Many people with a genetic suscepti-bility
to colon cancer never develop the disease, and we need to
figure out why. If we can recognize what protects those people
who are most susceptible, it should help us learn how to do
a better job preventing colon cancer in all populations."

Researchers elected to conduct the study in Israel because
three different ethnic populations there have very different
risks of colon cancer. Individuals of Ashkenazi Jewish descent
have relatively high rates of colon cancer, whereas colon
cancer is rare in people of Arabic descent. Sephardic Jews
have an intermediate risk of colon cancer.

"It is not clear why different populations within Israel
have such different risks of colon cancer, nor do we understand
the influences of immigration," says Gadi Rennert, M.D., Ph.D.,
co-principal investigator of the study and director of the
KHC National Center for Cancer Control at Carmel Medical Center
and Technion in Haifa, Israel. "This study should provide
insight into how cancer develops, not just within one specific
ethnic group, but how common themes can be unraveled for many
populations."

Previous studies have shown that more than one-half million
Ashkenazi Jews worldwide carry a specific genetic alteration
that doubles a person's risk of developing colon cancer. The
frequency of this genetic change, called I1307K, is uncommon
in Sephardic Jews and nearly non-existent in the Arabic population
of Israel.

I1307K does not directly cause colon cancer, but increases
susceptibility to cancer by destabilizing an important part
of a colon cancer gene. "I1307K seems to work like an oil
slick in the middle of this colon cancer gene," says Dr. Gruber,
who also serves as assistant professor of internal medicine
and epidemiology in the U-M Health System. "The machinery
that copies the cell's hereditary material (DNA) has a tough
time negotiating this part of the gene and frequently crashes."

Scientists can go back to this "crash site" and investigate
the scene of the accident to reconstruct exactly how a cancer
developed by looking at the DNA in the region where the damage
occurred. Study investigators hope to use this information
to help determine why some people manage this unstable region
more successfully than others.

Dr. Gruber and his colleagues believe there are probably
other similar genetic alterations that have yet to be discovered.
While most of the genetic alterations that have been discovered
appear to increase the risk of cancer, some genes may offer
some protection against cancer.

The study population will be drawn entirely from Israel
while the analyses will be conducted jointly in the United
States and Israel. In addition to studying how diet, lifestyle
and medications may differ in the cancer patients and the
comparison group, investigators also will perform a battery
of tests on the tumor samples using standard microscopes and
high-tech molecular tools that magnify genetic material.

"We would like to find better tools to lower the risk of
colorectal cancer with this study. Clarifying how genes, lifestyle
and environmental factors work together should give us these
tools, and hopefully we will have made another small step
toward preventing cancer," says Dr. Gruber.